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Studies Report Progress Understanding What Drives Repair of the Brain’s Insulating Myelin, Which is Damaged by MS

May 8, 2013

Researchers at the universities of Edinburgh and Cambridge, and at Stanford, have reported separate studies making inroads to understanding factors that stimulate the repair of myelin, the nerve insulation that is a target of multiple sclerosis. These important laboratory discoveries, supported in part by the National MS Society, are still in early stages and need to be confirmed and expanded, but they could eventually lead to promising new therapeutic approaches to stimulating myelin repair to restore function in people with MS. The studies were recently reported in the journals Brain and Nature Cell Biology.

Background: Multiple sclerosis attacks the brain and spinal cord, damaging the myelin coating on nerve fibers, and also the cells that make myelin, called oligodendrocytes. This disrupts nerve connections. Nerve fibers stripped of their myelin coating may become vulnerable to destruction. One approach to repairing myelin is to stimulate the body’s own healing capacity by uncovering the mechanisms involved in myelin regeneration.

There are pockets of spare, immature cells that reside in the brain and which can mature and serve as replacement oligodendrocytes capable of repairing damaged myelin. This natural healing process occurs in people with MS, but it is usually insufficient to overcome chronic damage.

Edinburgh/Cambridge Study: Drs. Tracy J. Yuen, Charles ffrench-Constant (MRC Centre for Regenerative Medicine, University of Edinburgh), Robin Franklin (University of Cambridge) and colleagues investigated an immune messenger protein called endothelin 2 and its potential role in stimulating myelin regeneration. They found it in high levels in areas of tissue damage (lesions) in brain samples from people who had MS in their lifetimes.

Through a series of studies involving tissues grown in dishes and the use of mouse models, they also found that endothelin 2 appears to stimulate myelin regeneration, as does a molecule that fits into its biological docking site. Although this is still in the basic discovery stage, this suggests a promising new therapeutic approach to stimulating myelin repair. The team was previously supported through the National MS Society’s Nervous System Repair initiative and now has Fast Forward support to test myelin repair strategies. (Read more) Their paper appeared in the April 2013 issue of Brain (136(4): 1035-1047).

Stanford Study: Drs. Victoria Rafalski, Peggy Ho, Lawrence Steinman, Anne Brunet and colleagues, funded in part by the National MS Society, explored the role of an enzyme called SIRT1, which is part of a family of proteins shown to inhibit the development of immature oligodendrocytes in late stages of development. Through a series of studies, they blocked the activity of SIRT1 and observed that more immature oligodendrocytes were formed both in lab dishes and in mouse models. They also found that mice whose SIRT1 was inactivated showed more robust myelin repair after damage. The researchers note that because SIRT1 has also been shown necessary for immune attacks to subside, and it also plays a role in nerve health, its future potential use in MS might require periodic use delivered to specific parts of the nervous system. This study was published in advance online on May 5, 2013 in Nature Cell Biology.

Next Steps: If their results are confirmed through further research, these basic laboratory studies provide important clues to mechanisms underlying myelin regeneration. These clues could eventually be translated to promising new therapeutic approaches to stimulating myelin repair to restore function in people with MS.

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system. Symptoms range from numbness and tingling to blindness and paralysis, and there is currently no cure for MS. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are leading to better understanding and moving us closer to a world free of MS. An estimated 1 million people live with MS in the United States. Most people with MS are diagnosed between the ages of 20 and 50, and it affects women three times more than men.


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